Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development

Jinliang Li, Tumul Srivastava, Ravindra Rawal, Edwin Manuel, Donna Isbell, Walter Tsark, Corinna La Rosa, Zhongde Wang, Zhongqi Li, Peter A Barry, Katharine D. Hagen, Jeffrey Longmate, Don J. Diamond

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-A*01/Kb Tg mice with rVV-SIVGag-Pol, the mice generated CD8+ T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/Kb Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.

Original languageEnglish (US)
Pages (from-to)16-28
Number of pages13
JournalVirology
Volume387
Issue number1
DOIs
StatePublished - Apr 25 2009

Keywords

  • Cellular immunity
  • Mamu A*01
  • Peptide vaccine
  • Poxvirus challenge
  • SIV
  • Transgenic mouse model

ASJC Scopus subject areas

  • Virology

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